Iva Tolic-Nørrelykke - Interior design of the cell

Previous and current research

A living cell is not a bag full of randomly distributed bits and pieces — molecules, molecular assemblies, and organelles. The cell interior is instead neatly organized in a dynamic yet controlled manner. Dynamic organization of the cell interior requires constant exploration of the intracellular space to adjust the position of cell components in a response to changes such as cell growth, progression through the cell cycle, and signals from the environment. To this aim the cell uses microtubules and actin filaments, motor proteins, and other cytoskeleton-associated proteins.

Nuclear oscillations

Motor proteins, exerting force on microtubules, position nuclei, spindles, and other organelles. Much is known about the behavior of individual motors in vitro. In vivo, however, a large number of motors act together. A key question is how a multitude of motors and microtubules organize their behavior into a concerted movement in a living cell.

In meiosis of fission yeast (and many other organisms), a multitude of motors generate large-scale oscillations of the nucleus. At the onset of meiosis, two cells of opposite mating types fuse at their tips forming a banana-shaped zygote. Subsequently, the two nuclei of the parental cells fuse into one, which starts to oscillate from one end of the cell to the other. These oscillations are crucial for proper chromosome pairing, recombination, and spore viability.

Meiotic nuclear oscillations. The spindle pole body is marked by asterisks, dynein is visualized in green and microtubules in red. Figure from Vogel, Pavin et al., PLoS Biol. 2009.


Nuclear oscillations are based on preferred detachment of dynein motors under high load force. During the nuclear movement, the load on the cortically anchored dynein motors on the leading microtubule is low. Thus, the motors remain attached and keep pulling the nucleus. Simultaneously, the load on the motors on the trailing microtubule is high, which enhances their detachment. Figure from Tolic-Norrelykke, Curr. Opin. Cell Biol., 2010.

Model system and methods
We study microtubule-based movements of the nucleus in the fission yeast Schizosaccharomyces pombe as a model system. An advantage of this system is its genetic amenability, which allows for fluorescent tagging and deletion of proteins involved in nuclear movements. Moreover, tracking and manipulation of single microtubules is possible due to the small number of microtubules in these cells. The cells are rod-shaped and the nuclear diameter is only slightly smaller than the diameter of the cell. Hence, one-dimensional models are appropriate theoretical descriptions of nuclear movements. Because of the low number of important degrees of freedom in the theoretical models, the underlying mechanisms can be easily understood.

We combine experimental methods (genetics, laser scanning microscopy, laser ablations, optical tweezers), advanced image analysis (e.g. automated particle tracking in MATLAB), and theoretical research (mathematical modeling, simulations) at the interface of physics and biology.

Future prospects and goals

To understand the physical basis as well as the molecular mechanisms of the dynamic architecture of cells.

Selected publications